Pharma Pipelines Filling, Firms Say; New Fear Is “Bottleneck” In Early Stage

Large pharma companies are facing a potential "bottleneck" in early stage clinical development as they sift through new therapeutic candidates, Merck Exec VP-Worldwide Basic Research Anthony Ford-Hutchinson, PhD, told a BIO-Windhover conference April 15 in Washington, D.C.

"I get a sense that most of the large pharma [companies] actually have a big increase in productivity in the early phase of discovery...and that can ultimately lead to a bottleneck in your preclinical area and clinical area," Ford-Hutchinson said.

The recent decline in new drugs reaching the market, along with a continued paucity of late-stage research projects, has been the dominant theme in discussions of big pharma pipelines for the past several years.

However, panelists at the BIO-Windhover conference suggested that the immediate challenge for large pharma companies now is managing a bumper crop of early stage projects flowing from the integration of genomics technology into drug discovery labs.

Ford-Hutchinson's comments about a potential bottleneck were echoed by AstraZeneca Global Discovery Research Head Jan Lundberg, PhD.

"There are some signs, I think, at least in the early phases of the R&D - that is, the output from discovery - that there is an increase in the number of compounds coming out," Lundberg said.

"The big challenge for all of us is to" translate the increase in candidates entering the clinic into "registration of new products."

Lundberg and Ford-Hutchinson spoke during a panel discussion focusing on what large pharma companies are looking for from biotech partners.

The glut of early stage compounds suggests one area of interest: partnership deals where a biotech firm can perform some of the sifting to identify the most promising leads.

One of Merck's "general principles" in partnering with biotechnology firms is to "kill compounds early when they need to be killed," Ford-Hutchinson said. Decisions are made easier by "new technologies" that "are not developed in-house in pharma and have to be brought in from other companies."

AstraZeneca's Lundberg suggested that "a symbiosis between big pharma and biotech will be needed" to make sure that the wealth of new leads produces commercial products.

The panelists expressed particular interest in working with partners who can use biomarkers to predict efficacy or identify safety issues before a decision is made to proceed with large scale studies.

As the Human Genome Project advances, interest in pharmacogenetic biomarkers is likely to increase. Pharmaceutical companies and FDA have begun working together to apply the technique in the regulatory process (see ¹ (Also see "Pharmacogenomics Moves Into Spotlight With Completion Of Genome Project" - Pink Sheet, 21 Apr, 2003.) ).

"Clearly, the key thing in this era of genomics revolution is to have a better understanding of disease pathophysiology," Lundberg said. Pharma companies will want to find "the relevant targets" to interfere with certain cell signals but not "influence normal function too much to cause side effects."

"And I think here we are expecting help both from biotechs and also from academia."

AstraZeneca has "seen great advantages in collaborating with biotechs" in "particularly lead generation and the screening area," Lundberg said. Here, biotechs can help identify "markers that can actually read signs that the new principles will work in patients."

Such "early read-outs" in the development process can lead to simplified clinical trials, Lundberg said.

Roche VP-Preclinical R&D Lee Babiss, PhD, agreed that "we have too many targets, too many hits associated with those targets, we can't screen them...and by outsourcing this work and working in partnership with biotechs, we're having a lot of success in this area."

However, Babiss added, Roche's large in-house diagnostics business gives the company an unusual profile for a pharma firm. "Because of our business interest in diagnostics," Roche tends to work on biomarker identification independently, he noted.

Merck's Ford-Hutchinson reported that, "most of what we're doing [on biomarkers] is internal."

One problem in working with partners on biomarker-based screening, he said, is that "valuing it from the external source is, I think, very difficult. The value of some of this biomarker technology, really what they're worth, that is a problem."

Lundberg suggested that an area for future pharma-biotech collaboration is predicting toxicology "by patterns of gene expressions or proteins."

Toxicity "is a major cause of problems for us when we try to discover new drugs, and the regulatory authorities are increasingly concerned about this whole issue."

"I think it's very important to collaborate with biotech partners, and really what we are looking for here are some biomarkers of early toxicology which you can see already in animal and healthy volunteers before you can take compounds into patients," he said.

Overall, the panelists suggested pharma has benefited from leveraging technologies developed by biotech. "I think they certainly help in reducing cycle time in early drug discovery," Ford-Hutchinson said. "The quality of the hits that emerge are better," Roche's Babiss added,

Lundberg took a more mixed stance. "Clearly we have invested in some technologies that...didn't pay off, and we've spent a huge amount of money on them," he said.

"The whole attitude now inside our company, and I'm sure also others, to new technology is much more mature in the sense that we want to see much more clearly the impact" from any outside investments, he said.